Increased Interferon Stimulated Gene (ISG) Expression Linked to Neutrophil Dysfunction in ARDS

Increased interferon gene expression could result in neutrophil dysfunction and cause variability in outcomes in patients suffering from ARDS.

Adult Respiratory Distress Syndrome (ARDS) is a condition where the patient suffers from breathlessness, low blood oxygen levels and lung inflammation that could progress to respiratory failure. It is caused by a number of conditions like sepsis, bacterial pneumonia, severe trauma, multiple transfusions, aspiration of gastric contents, drug overdosage and post cardiopulmonary bypass surgery.

White blood cells, called neutrophils, accumulate in the lungs during ARDS. They help to fight against infection, but could also contribute to inflammatory damage in the lungs.

Causes of Acute Respiratory Distress Syndrome (ARDS)
Severe sepsis and bacterial pneumonia are among the most common causes of ARDS.

Different people are affected to variable extents by ARDS. Certain factors like genetic, environmental and complex demographic factors are known to be responsible for this heterogenicity. Researchers now suggest that a variable expression of interferon - stimulated genes (ISGs) could also be responsible for the variable response in ARDS patients.

Viral infections result in an increased production of interferons due to increased expression of interferon- stimulated genes (ISG). Interferons are proteins that play an important role in the inflammatory process. Researchers suggest that increased expression of ISGs alters neutrophil functions and impairs their ability to fight against bacterial infection. During this study, this impaired defense was observed against Staphylococcal aureus but not Pseudomonas aeruginosa.

Thus, patients with high ISGs post ARDS could be increasingly susceptible to infections caused by S aureus bacteria. On the other hand, patients with low expression of ISGs may be less susceptible to this infection. Thus, ISG expression could explain the variability in patients suffering from ARDS –associated complications.

Thus, besides the already known genetic, environmental, and complex demographic factors, increased ISG expression may also be responsible for the variability of neutrophil response in ARDS.

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1. Malcolm KC, Kret JE, Young RL, Poch KR, Caceres SM, et al. (2011) Bacteria-Specific Neutrophil Dysfunction Associated with Interferon-Stimulated Gene Expression in the Acute Respiratory Distress Syndrome. PLoS ONE 6(7): e21958. doi:10.1371/journal.pone.0021958

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